Cemiplimab Monotherapy Continues to Generate Responses in Locally Advanced or Metastatic CSCC

Single-agent cemiplimab (Libtayo) demonstrated safety and efficacy in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who comprised group 6 of the phase 2 EMPOWER-CSCC-1 trial (NCT02760498) that was in line with what was previously reported in groups 1, 2, and 3 of the study.¹

Data presented at the 2022 ESMO Congress showed that at a median follow-up of 8.71 months (range, 0.0-19.5), evaluable patients from group 6 (n = 164) achieved an ORR of 45.1% (95% CI, 37.4%-53.1%) with the agent, which included a complete response rate of 5.5% and a partial response rate of 39.6%.

“Cemiplimab remains a standard-of-care option in patients with advanced CSCC who are not candidates for curative surgery or radiation,” lead study author Brett Hughes, MD, an associate professor at the Prince Charles Hospital Northside Clinical Unit, faculty of Medicine, at the Royal Brisbane and Women’s Hospital, the University of Queensland, in Brisbane, Australia, and colleagues, wrote in a poster presentation of the data. 

In September 2018, the FDA approved cemiplimab for the treatment of patients with metastatic CSCC or those with locally advanced CSCC who are not candidates for curative surgery or radiation.² The regulatory decision was based on previously reported findings from the EMPOWER-CSCC-1 trial. At the 2022 ESMO Congress, additional safety and efficacy data were presented from group 6 of the trial, which included 167 patients who were at least 18 years of age and had histologically confirmed metastatic or unresectable locally advanced CSCC.

Study participants received 350 mg of intravenous cemiplimab once every 3 weeks for up to 108 weeks. Notably, patients had the option to switch to subcutaneous dosing.

The primary end point of the trial was ORR per independent central review. Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS) per central and investigator review, as well as safety and tolerability.

Among the 167 enrolled patients, the median age was 76 years (range, 40-94). Most patients were male (77.8%) and had a primary cancer site of the head and neck (67.7%). Patients had an ECOG performance status of either 0 (40.1%) or 1 (58.7%). Furthermore, 59.9% of patients presented with metastatic CSCC, and 40.1% had locally advanced disease. Five patients previously received systemic treatment.

A total of 164 patients were evaluated for response; 2 patients did not receive cemiplimab and 1 patient did not have a baseline tumor assessment because of COVID-19. The median duration of exposure to cemiplimab was 35.7 weeks (range, 0.9-86.9), and the median number of doses administered was 11 (range, 1-29).

As of a data cutoff date of October 25, 2021, the median DOR was not yet reached (95% CI, 13.0–not evaluable [NE]). The median PFS was 14.7 months (95% CI; 10.4-NE), and the median OS was not reached (95% CI; 17.6-NE).

Regarding safety, 98.8% of patients treated with at least 1 dose of cemiplimab experienced at least 1 any-grade treatment-emergent adverse effect (TEAE). The most common any-grade TEAEs were fatigue (26.1%), diarrhea (21.2%), pruritus (21.2%), nausea (17.0%), asthenia (13.9%), arthralgia (13.3%), constipation (11.5%), decreased appetite (11.5%), and maculopapular rash (10.3%).

Grade 3 or higher TEAEs occurred in 45.5% of patients, and the most common ones experienced with the agent included hypertension (3.6%), pneumonia (3.6%), and general physical health deterioration (3%).

Any-grade serious TEAEs and grade 3 or higher serious TEAEs were reported in 43.6% and 34.5% of patients, respectively. Any-grade TEAEs leading to treatment discontinuation were reported in 13.9% of patients; 7.3% of patients discontinued due to grade 3 or higher TEAEs.

TEAEs resulted in death for 8.5% of patients. However, no deaths were deemed to be related to cemiplimab. The 14 fatal AEs were due to COVID-19–related events (n = 2), other infection (n = 4), sudden death not otherwise specified without autopsy (n = 2), and 1 instance each of myocardial infarction, gastrointestinal bleed, pulmonary embolism, acute myelogenous leukemia, declining mental status in setting of morphine patient-controlled analgesia and pulmonary oedema, and meningitis that was likely infectious.

References

1. Hughes BGM, Grob JJ, Bowyer SE, et al. Phase 2 confirmatory study of cemiplimab (350 mg IV Q3W) in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Study 1540 group 6. Ann Oncol. 2022;33(suppl 7):S921. doi:10.1016/j.annonc.2022.07.944
2. FDA approves first treatment for advanced form of the second most common skin cancer. New release. FDA. September 28, 2018. Accessed October 24, 2022. https://bit.ly/3SyYumG